The worldwide prevalence of nonalcoholic fatty liver disease (NAFLD) has increased along with that of obesity over the last decades. In fact, the global prevalence of NAFLD is around 25%, and it has become the most prevalent chronic liver disease in India also due to its strong association with obesity and lack of physical exercise. Different research reports too peg a prevalence rate of around 20 -25% for Indian population. The rise in the prevalence of these conditions seems to be largely explained by the exposure to an “obesogenic” environment. This complex and multidimensional scenario is composed of diverse factors that promote an individuals’ overall energy imbalance (i.e., towards a sustained positive energy balance) such as; increased availability (food supply) and overconsumption of low-nutrient, energy-dense foods; Food these days is available ‘On Tap’ thus fueling conditions like Obesity and NAFLD modern sedentary lifestyle, among others, leading a state of excess adiposity Obesity represents the centerpiece in the development of several metabolic complications such as insulin resistance, diabetes mellitus type 2 (T2DM), cardiovascular disease (CVD), and NAFLD MAFLD – Non-alcoholic Fatty Liver Disease is a multifactorial metabolic disorder in which excessive intrahepatic fat accumulation is the hallmark feature. Occasionally, liver fat is accompanied by inflammation that causes more drastic morphological changes in the liver tissue. It is important to remark that besides over-nutrition, certain types of undernutrition paradoxically may promote the development of fatty liver. Grades / Stages of NAFLD NAFLD encompasses a wide spectrum of liver damage that is categorized by histological examination. The least advanced stage of disease, simple steatosis (SS), is characterized by steatosis alone (defined as >5% hepatocytes containing lipid vesicles). Nonalcoholic steatohepatitis (NASH), which represents a more severe form of NAFLD, is defined by the presence of marked inflammation and hepatocyte ballooning with or without fibrosis. NAFLD is a progressive disease, in which chronic hepatic inflammation is involved in the evolution of NASH to cirrhosis that represents a risk factor for the development of hepatocarcinoma. How to Manage NAFLD and Hopefully Reverse NAFLD Healthy lifestyle modifications, namely diet and physical activity, are the mainstay of the NAFLD therapy and nor so much drugs. NAFLD is part of a complex network of metabolic disruptions in multiple tissues commonly associated with obesity, which consequently makes diet therapy a difficult endeavor. The present tendency of nutritional intervention leans towards correcting unhealthy dietary factors that promote disease progression. Currently, the optimal nutritional management remains debatable, although there is general consensus that gradual body weight loss is the recommended standard of care for the treatment of NAFLD. Dietary energy restriction is a key element to achieve weight reduction, but its compliance depends largely on self-control, and consequently, diet adherence might become quite challenging in most cases. Hence, different choices of nutritional interventions have been explored in the NAFLD context. This write is meant to serve as a comprehensive overview of the most relevant literature describing nutritional/dietary approaches for the management of NAFLD. Clinical Practice Guidelines – Target Weight Loss American Association for the Study of Liver Diseases (AASLD) recommends a total weight reduction of at least 3–5% to ameliorate steatosis, whereas improving most of the histopathological features requires a greater degree of weight loss (7–10%). The European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), and European Association for the Study of Obesity (EASO) suggest a 7–10% of total weight loss target. The EASL-EASD-EASO also advises the use of structured programs aimed at lifestyle changes. EASL-EASD-EASO AASLD-ACG-AGA Energy Intake REDUCE by 500 -1,000 Kcal/Day REDUCE by 500 -1,000 Kcal/Day Macro-Nutrient Composition 4 Diet Types Low to Moderate Fat Moderate to High Carbohydrate Low Carbohydrate Ketogenic Diets Mediterranean Diet Not Specified Omega-3 Fatty Acids may be considered to treat Hypertriglyceridemia in NAFLD Patients Fructose Intake Avoid drinks and foods with Fructose and added Fructose/ HFCS Not Specified Alcohol Intake Strictly keep below daily limit of 30 g for Men and 20 g for Women NAFLD Patients should not consume heavy amounts of Alcohol Micro-Nutrients Short Term usage of Vit E at 800 IU/Day strictly in non-cirrhotic, non-diabetic NAFLD Patients Short Term usage of Vit E at 800 IU/Day strictly in non-cirrhotic, non-diabetic NASH Patients Body Weight Loss Recommendations 7–10% total weight loss target in Obese / Overweight NAFLD cases 3–5% total weight loss appears essential in NAFLD cases 7–10% total weight loss target is needed to improve histopathological features in NASH, including fibrosis Exercise / Physical Activity 140 – 200 Minutes/ week of moderate intensity aerobic physical activities in 3 to 5 sessions are preferred, including brisk walking, cycling and jogging Resistance training has shown benefits in promoting Musculo-skeletal strength which helps in metabolic diseases such as NAFLD Moderate intensity exercise regularly AASLD – American Association for the Study of Liver Diseases; ACG – American College of Gastroenterology; AGA – American Gastroenterology Association; EASL – European Association for the Study of the Liver; EASD -European Association for the Study of Diabetes and; EASO -European Association for the Study of Obesity NAFLD – Plant-based nutraceuticals Ascophyllum nodosum and Fucus vesiculosus (GDUE®) GDUE® is a nutraceutical obtained from the brown algae Ascophyllum nodosum and Fucus vesiculosus at a ratio of 95/5; each capsule contains 237.5 mg of Ascophyllum nodosum extract, 12.5 mg of Fucus vesiculosus and 7.5 μg of chromium. Ascophyllum nodosum and Fucus vesiculosus are rich in natural substances that can slow down cholesterol absorption by increasing intestinal viscosity and also reduce sugar absorption through the inhibition of the α-amylase and α-glucosidase enzymes. It has already been reported that this inhibitory effect is due to the high content of some bioactive compounds, such as polysaccharides, polyphenols, and fatty acids. Polyphenols act on post-prandial hyperglycemia by slowing down the absorption of carbohydrates. Several studies on GDUE® have reported improvements in parameters correlated with NAFLD. De Martin et al. demonstrated a reduction in HOMA-IR, waist circumference, fasting blood glucose, and insulin levels in overweight or obese patients treated with GDUE®, a capsule taken three times per day before meals for 6 months. Silymarin Silymarin is an anti-oxidant agent obtained from milk thistle and at present, silymarin is one of the most-used natural compounds in the treatment of liver
Vitamin C: How a Common Supplement Reshapes Your Gut Microbiome
Vit C Deficiency – Worldwide Issue Low vitamin C concentrations have been reported in cognitively impaired patients, such as those with Alzheimer’s disease and dementia, and in advanced cancer and severe respiratory tract infections including SARS-CoV-2 infection. Between 0.8 and 26% of adults in high-income countries appear to be vitamin C deficient, as defined by levels <11 μmol/l. A US survey found that about 13% of the population was deficient, with the overall occurrence of age-adjusted vitamin C deficiency being closer to 7% and higher among lower socioeconomic classes. However, it has also been suggested that because depletion of tissue stores can happen rapidly, short-term or intermittent vitamin C deficiency prevalence in the population could be much higher. Vitamins – Modulation of Gut Microbiome An increasing body of evidence has shown that the gut microbiome is a key regulator of immunity and host defense mechanisms. Disturbance of homeostasis involving interactions between the gut microbiome and the immune system can adversely influence resistance to viral infections, increase disease risk and alter neurocognitive function. Although previous studies have recognized that vitamin supplementation can alter the gut microbiome, no vitamins are presently classified as prebiotics (agents that promote the growth of beneficial microorganisms in the gut) by the International Scientific Association for Probiotics and Prebiotics. Vitamin supplementation in patients with Crohn’s disease resulted in an altered gut microbiome composition when patients were administered riboflavin or vitamin D [36]. Several additional studies on vitamin D and the gut microbiome have been performed linking the mucosal immune system and the microbiome in inflammatory bowel disease, identifying host–microbe interactions and mutations in the vitamin D receptor as risk factors for inflammatory bowel disease and suggesting that the vitamin D receptor can affect the gut microbiome. A recent study by Pham and colleagues compared the effects of colon-targeted vitamins C, B2 and D on the human gut microbiome and reported that vitamin C produced the most distinct effect on the microbiome, increasing microbial alpha-diversity and short-chain fatty acids. A large variety of factors act to shape and potentially disrupt individuals’ microbiomes, such as genetics, aging, diet, infections and medications. Team of Researchers led by Dr Sabine Hazan hypothesized that vitamin C administration could modulate the gut microbiome, which is a known regulator of immunity. It is possible that such microbiome changes could contribute to protection from viral illnesses associated with microbiome changes, including SARS-CoV-2 infection, and this is worthy of exploration. Vit C – New Publication shows promise in Improving Gut Microbiota Diversity A clinical discovery by Dr. Sabine Hazan has uncovered a powerful new function of Vitamin C. Beyond its well-known antioxidant role, it appears to be a critical fuel for our beneficial gut bacteria. Dr Sabine and Team carried out an extensive Observational Study in 23 participants who received Vit C supplementation from 3 g / day to 25 g/week, for a period of5 days to 10 days. The findings now published have demonstrated that oral usage of Vit C significantly increases Bifidobacteria levels in gut. The results indicate that vitamin C increases the abundance of gut bacteria of the genera Bifidobacterium. An earlier study by Otten et al. investigated vitamin C supplementation at a dose of 1 g per day for 2 weeks. They also observed a more than fourfold increase in the mean relative abundance of Bifidobacterium, supporting these new findings by Dr Sabine and her Team Bifidobacteria – Why does this matter Bifidobacteria are not passive residents; they are vital for: – Building a robust immune system – Fortifying the gut lining – Combating chronic inflammation – Synthesizing essential nutrients. Members of the genus Bifidobacterium are considered beneficial bacteria and are an indicator of a healthy gut. Bifidobacterium are among the first microbes to colonize the human gastrointestinal tract and are used as probiotics due to their health-promoting properties. This research suggests that one of Vitamin C’s most profound benefits may be its prebiotic-like effect, nurturing the microbiome that forms the foundation of our overall health. It’s a paradigm shift in understanding how a simple, accessible nutrient works from the inside out. Conclusion Vitamin C as a therapeutic agent should be explored specifically for its potential to reverse or ameliorate disorders linked to microbiome dysbiosis, especially Bifidobacterium deficiencies. It may be able to restore the gut microbiome (i.e. carry out Refloralization) after Bifidobactrium depletion due to various conditions or acute illness, including respiratory viral illnesses such as SARS-CoV-2 infection.
Vit B12 – Why Indians Have Abysmally Low Levels and What are Serious Implications
Vitamin B12 is an essential vitamin but is available largely from non-vegetarian sources only. Indian population, with invariably largely vegetarian food habits, is more prone to have deficiency of vitamin B12. Vitamin B12 deficiency is extremely widespread in India, with some studies suggesting up to 75% of the population may be affected, particularly due to a largely vegetarian diet. Other contributing factors include diet, demographic and religious variations, and lifestyle elements like stress, poor gut health, and alcohol consumption. Prevalence and affected groups High prevalence: Some studies estimate that around 75% of the Indian population suffers from some level of B12 deficiency. Other studies show variable prevalence rates, ranging from 16% to 77% across different demographics Vegetarians: Vegetarians and especially vegans are at a higher risk because the best sources of vitamin B12 are animal products like meat, eggs, and dairy Pregnant women: A high prevalence has been observed in pregnant women in rural India Urban corporate employees: A recent study found over 57% of male corporate employees had B12 deficiency, with nearly 50% of women also affected Children: Deficiency is prevalent in children, with rates varying by age group Symptoms of Vit B12 Deficiency Fatigue and weakness Tingling or numbness (paresthesias) Mood changes, irritability, depression, or memory problems Tongue problems, such as swelling and redness Weakened immune system – prone to diseases Vit B12 – Levels in Indians, abysmally low Data from a large number of pathology labs indicates that Most Indians have Vit B12 levels between 150–250 pg/mL – a range where neurological damage may already start happening. Newer Research and publications (Lindenbaum J, Healton EB, Savage DG, et al) demonstrate that shows that metabolic and nerve abnormalities may occur even at Vit B12 levels below 400–450 pg/mL. Chronic low Vitamin B12 quietly destroys nerves and brain health, sample the data – MMA rises 200–300%, Homocysteine levels are elevated by 30–50% which is a significant cardiac risk marker, neuropathy risk shoots up below 200 pg/mL and spinal-cord damage becomes likely below 150 pg/mL. Among Diabetics – 1 in 3 long-term Metformin users and 20–50% of diabetes patients are already deficient in Vit B12. Although Vit B12 being a water soluble vitamin requires regular intakes, our Liver does store Vit B12 and hence the deficiency does not manifest quickly. However, over a period of time some of early signs start appearing and after 2–3 years of continued deficiency, nerve damage may start becoming permanent. Solution Getting Vit B12 from diet remains one of the best, inexpensive source as dietary Vit B12 is more bioavailable and hence usable by body. If anything, Vit B12 deficiency may prompt some Indians to shun vegetarianism and nudge them to include kheema -kalezi in their plates. Supplementation remains only a second best option and focus should be on using high quality, non-cyanocobalamins and using a better alternate in Methyl-cobalamin. The suggested, targeted levels for Indians is to have Vit B12 levels exceeding >600 pg/mL for healthier life and for long-term neurologic protection.
Magnesium Supplementation – Helps REDUCE Blood Pressure; Clinical Evidence
Systemic hypertension, also known as High Blood Pressure / BP – is a persistent elevation of the systemic arterial blood pressure (BP), and is a highly prevalent condition and a major independent risk factor of mortality and cardiovascular disease. Preventing and treating hypertension has become a significant factor in decreasing the risk and burden of various diseases, thus reducing disease-related mortality. However, inadequate management of BP still remains one of the greatest individual risk factors of all-cause mortality globally, and each 10 mmHg rise in average systolic blood pressure (SBP) has been previously associated with an increase in cardiovascular disease (CVD) and chronic kidney disease risk by up to 16%. Dietary and lifestyle modifications play major role in managing BP. Magnesium plays an important role in blood pressure regulation, as demonstrated by its influence on endothelial function, calcium efflux, and oxidative stress. Magnesium deficiency can contribute to endothelial dysfunction, increased oxidative stress, and vascular remodeling, all of which exacerbate hypertension and cardiovascular disease risk. Role of Magnesium in Blood Pressure Regulation Magnesium is the fourth most common cation in the human body, and a deficient intake of magnesium has been associated with various diseases, including asthma, diabetes mellitus, hypertension, stroke, heart disease, hypertension, and even cancer. Therefore, magnesium has been proposed as a treatment for hypertension. By inducing the formation of nitric oxide and prostacyclin, magnesium helps in modulating vasodilation, decreasing vascular tone and vascular reactivity. Magnesium also possesses anti-inflammatory and as antioxidant properties and interacts with calcium, decreasing peripheral vascular resistance and thus decreasing blood pressure Supplementation with magnesium has been shown to induce vasodilation, decrease vascular tone, and improve blood pressure outcomes. Magnesium Helps Reduce BP – Clinical EVIDENCE A recent umbrella meta-analyses (PMID: 39280209) found that magnesium doses ≥400 mg/day, administered for a duration of ≥12 weeks, can significantly reduce both systolic and diastolic blood pressure (SBP: -6.38 mmHg; DBP: -3.71 mmHg) – mostly in people with previous metabolic disorder (and also likely to have inadequate magnesium status before supplementing). Mechanistically, magnesium influences nitric oxide production, prostaglandin synthesis, and calcium channel function, which collectively promote vasodilation and attenuate blood pressure increases. Magnesium is one of the most common minerals in the human body, with 99% of it distributed intracellularly. The role of magnesium in reducing hypertension has been attributed to multiple mechanisms of action, including acting as a calcium channel blocker, competing with sodium binding sites on vascular smooth muscle cells, decreasing intracellular sodium and calcium, enhancing prostaglandin E, binding cooperatively with potassium, inducing vasodilation, improving endothelial dysfunction in diabetic and hypertensive patients. Moreover, magnesium induces nitric oxide release from endothelial cells, which acts as vasoactive mediator and produces a synergistic effect with antihypertensive medications. Magnesium Supplementation – Clinical Usage In practice, ensuring sufficient magnesium intake may offer long-term cardiovascular benefits, especially when integrated into a broader strategy (as magnesium alone is not strong enough to function as a “monotherapy” for treating hypertension) targeting endothelial health, oxidative stress reduction, and vascular integrity. A daily supplementation of good quality, chelated, highly bio-available Magnesium at 400 mg/day should be the starting point. “> Systemic hypertension, also known as High Blood Pressure / BP – is a persistent elevation of the systemic arterial blood pressure (BP), and is a highly prevalent condition and a major independent risk factor of mortality and cardiovascular disease. Preventing and treating hypertension has become a significant factor in decreasing the risk and burden of various diseases, thus reducing disease-related mortality. However, inadequate management of BP still remains one of the greatest individual risk factors of all-cause mortality globally, and each 10 mmHg rise in average systolic blood pressure (SBP) has been previously associated with an increase in cardiovascular disease (CVD) and chronic kidney disease risk by up to 16%. Dietary and lifestyle modifications play major role in managing BP. Magnesium plays an important role in blood pressure regulation, as demonstrated by its influence on endothelial function, calcium efflux, and oxidative stress. Magnesium deficiency can contribute to endothelial dysfunction, increased oxidative stress, and vascular remodeling, all of which exacerbate hypertension and cardiovascular disease risk. Role of Magnesium in Blood Pressure Regulation Magnesium is the fourth most common cation in the human body, and a deficient intake of magnesium has been associated with various diseases, including asthma, diabetes mellitus, hypertension, stroke, heart disease, hypertension, and even cancer. Therefore, magnesium has been proposed as a treatment for hypertension. By inducing the formation of nitric oxide and prostacyclin, magnesium helps in modulating vasodilation, decreasing vascular tone and vascular reactivity. Magnesium also possesses anti-inflammatory and as antioxidant properties and interacts with calcium, decreasing peripheral vascular resistance and thus decreasing blood pressure Supplementation with magnesium has been shown to induce vasodilation, decrease vascular tone, and improve blood pressure outcomes. Magnesium Helps Reduce BP – Clinical EVIDENCE A recent umbrella meta-analyses (PMID: 39280209) found that magnesium doses ≥400 mg/day, administered for a duration of ≥12 weeks, can significantly reduce both systolic and diastolic blood pressure (SBP: -6.38 mmHg; DBP: -3.71 mmHg) – mostly in people with previous metabolic disorder (and also likely to have inadequate magnesium status before supplementing). Mechanistically, magnesium influences nitric oxide production, prostaglandin synthesis, and calcium channel function, which collectively promote vasodilation and attenuate blood pressure increases. Magnesium is one of the most common minerals in the human body, with 99% of it distributed intracellularly. The role of magnesium in reducing hypertension has been attributed to multiple mechanisms of action, including acting as a calcium channel blocker, competing with sodium binding sites on vascular smooth muscle cells, decreasing intracellular sodium and calcium, enhancing prostaglandin E, binding cooperatively with potassium, inducing vasodilation, improving endothelial dysfunction in diabetic and hypertensive patients. Moreover, magnesium induces nitric oxide release from endothelial cells, which acts as vasoactive mediator and produces a synergistic effect with antihypertensive medications. Magnesium Supplementation – Clinical Usage In practice, ensuring sufficient magnesium intake may offer long-term cardiovascular benefits, especially when integrated into a broader strategy (as magnesium alone is not strong enough to function as a “monotherapy” for treating hypertension) targeting endothelial health, oxidative stress reduction, and vascular integrity. A daily supplementation of good quality, chelated, highly bio-available Magnesium
Selenium – Most Overlooked Anti-Oxidant Mineral, Must for THYROID Patients
Selenium is an essential trace element vital for thyroid function, and its deficiency is a risk factor for various thyroid disorders, including hypothyroidism. While many studies suggest benefits, international clinical guidelines do not yet recommend routine selenium supplementation for all patients with hypothyroidism, with the key exception of those with mild Graves’ orbitopathy (eye disease). Role in Thyroid Function and Hypothyroidism Thyroid Hormone Metabolism: Selenium is a key component of selenoproteins, including iodothyronine deiodinases (DIOs), which are enzymes that regulate the activation and deactivation of thyroid hormones. Specifically, DIO1 and DIO2 convert the inactive thyroxine (T4) into the active triiodothyronine (T3). Antioxidant Defense: The thyroid gland produces hydrogen peroxide (H₂O₂) to synthesize thyroid hormones, a process that generates a high degree of oxidative stress. Selenium-dependent glutathione peroxidases (GPx) act as antioxidants to neutralize excess H₂O₂, protecting thyroid cells from damage. Immune Modulation: Selenium also modulates the immune system. In autoimmune thyroid conditions like Hashimoto’s thyroiditis (the most common cause of hypothyroidism), selenium deficiency can worsen inflammation, while supplementation may help regulate immune responses and reduce autoantibody levels. Efficacy and Clinical Use of Selenium During a three-month study with 70 women with Hashimoto’s antibodies, all were dosed with T4 to maintain TSH in the normal range; half were given 200 mcg of sodium selenite (selenium) per day for three months, and the remainder were given a placebo. At the end of the experiment, 25% of patients in the selenium group had normal antibodies, compared with 6% of the placebo group. Thyroid ultrasound confirmed normal gland structure in those with normal antibodies. That’s a 4x remission rate with supplementation. The TPO antibody decreased by 34% in the selenium group, almost three times the reduction seen in the other group (12%). TGA antibodies didn’t change in the selenium group but did decrease in the placebo group. TSH, fT3, and fT4 (thyroid hormones) were unchanged – remember, all participants were given T4, which was dosed to “normalize” TSH. “We conclude that selenium substitution may improve the inflammatory activity in patients with autoimmune thyroiditis, especially in those with high activity. Whether this effect is specific for autoimmune thyroiditis or may also be effective in other endocrine autoimmune diseases has yet to be investigated.” Clinical Evidence – 2 In a case study, one woman with Hashimoto’s was given 50-100 mcg of supplemental selenium per day for 14 months. 50 mcg had little effect, but 100 mcg was effective. At that dose, TPO antibodies decreased by 76%. Then, supplementation was stopped, and the woman was tested over the next five months… her TPO antibodies increased. “After withdrawal of the supplementation, the sharp fall of Se and GPX3 promptly occurred, and this phenomenon was accompanied with a marked increase in TPOAb.” Selenium Modulates Immune System Though selenium is needed for thyroid hormone conversion, most of its benefits in thyroid disease likely stem from its immune-modulating properties and effects on ROS in the thyroid gland. It is noted to even reduce the likelihood of postpartum thyroiditis/Hashimoto’s. “Most authors attribute the effect of supplementation on the immune system to the regulation of the production of reactive oxygen species and their metabolites. In patients with Hashimoto’s disease and in pregnant women with anti-TPO antibodies, selenium supplementation decreases anti-thyroid antibody levels and improves the ultrasound structure of the thyroid gland. Although clinical applications still need to be defined for Hashimoto’s disease, they are very interesting for pregnant women given that supplementation significantly decreases the percentage of postpartum thyroiditis and definitive hypothyroidism.” Selenium may help with autoimmune hyperthyroidism, too. Patients given a combination of antioxidants, including selenium, achieve normal thyroid hormone levels more rapidly than those who were not. Both groups were also taking anti-thyroid medicatio Selenium for Graves’ Patients Normal thyroid status in Graves’ patients is correlated with blood selenium levels. Patients with Graves’ orbitopathy (thyroid eye disease) fare better when given selenium (sodium selenite, 200 μg/day). “More than 70% of patients treated with selenium reported an improvement in quality of life vs 22% of patients receiving placebo. Orbital lesions were improved in 61% of patients receiving selenium vs 35% of patients treated with placebo. They worsened in 7% of patients treated with selenium vs 26% of patients receiving placebo.” Supplementing selenium (500 mcg/day) during acute stress (in this case, during a stay in the surgical ICU) accelerates the recovery of normal thyroid hormone levels, both T4 and T3. Selenium with Myo-Inositol – a Powerful Combo Combining selenium and myo-inositol reduces thyroid antibodies, lowers TSH, and increases thyroid hormones in people with hypothyroidism. The combination also increased TSH in a hyperthyroid patient – it seems to normalize rather than simply increase thyroid function. Selenium and Myo-inositol are important for thyroid hormone synthesis, and low levels may predispose to the development of hypothyroidism. People with hypothyroidism have a higher demand for myo-inositol. Study 1: “In the present study, we were able to demonstrate that, in subclinical hypothyroidism, patients with autoimmune thyroiditis, treated with Myo-Inositol and selenomethionine, experience a reduction of the increased TSH that selenomethionine supplementation alone was not able to promote. Concomitantly, the concentration of the two autoantibodies declined in both groups.” Study 2: “TSH, TPOAb, and TgAb antibody levels were significantly decreased in patients treated… a significant fT3, and fT4, increase, along with an amelioration of their quality of life, was observed. Remarkably, TSH values of the hyperthyroid patient increased from 0.14U/ml up to 1.02U/ml, showing a complete restoration of TSH values at a normal range.” Natural Sources of Selenium Most people can meet their daily requirement of 55 mcg by eating a balanced diet. Rich food sources include: Brazil nuts (an extremely rich source, often containing more than the daily requirement in a single nut) Seafood (tuna, sardines, shrimp) Meat (Goat, Lamb, chicken, turkey) Eggs and dairy products Grains and cereals There is 83 μg of selenium in: 2 oz oysters, or 3 large eggs, or 10 oz mushrooms and there is 600 mg of myo-inositol in: 12 oz cantaloupe, or 15 oz orange, or 30 oz mandarin
MAGNESIUM – Why Supplementation is a MUST in Sleep Disorders
Current guidelines recommend that adults maintain optimal health and daytime performance by achieving a minimum of 7 hours of total sleep per night with a sleep efficiency of at least 85%. Sleep Disorders – Global Status Notably, a comprehensive global survey encompassing participants aged 15–65 highlights a significant prevalence of sleep disorders. In the United States, 56% of respondents reported experiencing sleep disturbances, with 55–69% of those affected struggling with sleep initiation, 63–78% facing sleep maintenance issues, and 31–52% reporting poor overall sleep quality. Similar trends were observed in Western Europe (31%) and Japan (23%), indicating that sleep disorders represent a widespread public health concern across different regions. Impairments in sleep quantity and quality can manifest as symptoms of sleep disorders, such as daytime somnolence, excessive daytime sleepiness, and nocturnal snoring. Magnesium exerts a critical role in the physiological regulation of sleep-modulating substances Magnesium (Mg), the second most abundant mineral in the human body, participates in over 300 biochemical reactions. Serving as an essential cofactor for numerous enzymatic reactions, it plays a pivotal role in maintaining cellular functions and physiological homeostasis. Magnesium is pivotal to a wide array of biological processes, including oxidative phosphorylation, energy generation, glycolysis, and the biosynthesis of proteins and nucleic acids. Magnesium ions also participate in muscle contraction, control neuronal excitability, and influence neurotransmitter cycling by regulating the transmembrane transport of other ions. This role is particularly crucial in the regulation of sleep.4 Magnesium in Melatonin and Serotonin Production Several studies have demonstrated that magnesium deficiency in rats results in a reduction in plasma melatonin concentrations. Magnesium is closely related to the production of melatonin. As a well-investigated and widely utilized sleep-promoting hormone, melatonin is a key regulator of the sleep-wake cycle and exhibits potent antioxidant properties. An increase in oxidative stress may account for, at least in part, the poor sleep quality. Melatonin can enhance the activity of superoxide dismutase, thereby preventing oxidative stress-induced damage to cell membranes. When combined with omega-3 fatty acids, melatonin exerts an antioxidant effect by significantly enhancing superoxide dismutase activity in the human body. Furthermore, endogenous melatonin has been shown to attenuate the excitatory neurotransmitter effects of L-glutamate by inhibiting specific NMDA receptor binding sites, thus promoting sleep. Magnesium can also enhance the activity of serotonin N-acetyltransferase—an enzyme critical for melatonin synthesis. Physiologically, magnesium interacts with the synthesis of serotonin and melatonin. Serotonin is an intermediate product in the production of melatonin, and melatonin is a metabolite of serotonin. The production of melatonin requires serotonin, and a deficiency or excess of serotonin can exert an impact on sleep duration and quality. Magnesium also helps monoamine substances (such as serotonin) bind to their respective sites. The commonly discussed mechanism for increasing sleep duration is the pathway that promotes serotonin synthesis. Serotonin regulates most brain functions—including the sleep cycle—either directly or indirectly. Typically, serotonergic neurons collectively innervate numerous brain regions involved in sleep-wake behavior, functioning to promote consciousness and inhibit sleep. 5-hydroxytryptophan is generated from tryptophan through the catalysis of tryptophan hydroxylase and then converted into serotonin by the catalysis of 5-hydroxytryptophan decarboxylase. Tryptophan is a precursor to the neurotransmitter serotonin and the neurosecretory hormone melatonin, both of which are associated with sleep and alertness. Tryptophan can also regulate sleep and the circadian rhythm by increasing melatonin levels. Magnesium in Insomnia Insomnia stands as the most prevalent sleep disorder. According to the International Classification of Sleep Disorders, the diagnosis of insomnia includes difficulties in initiating sleep, maintaining sleep, and subsequent impairment of daytime functioning. In a human study, it was observed that long-term sleep deprivation decreased intracellular magnesium content and reduced exercise tolerance, which could subsequently be corrected through oral magnesium supplementation. Nielsen et al conducted a study investigating the role of magnesium supplementation in adult sleep disorders, and following 7 weeks of treatment with 320 mg/day of magnesium citrate, patients exhibited an overall improvement in their PSQI scores. Abbasi et al aimed to examine the effects of magnesium on insomnia in elderly individuals, and he administered 500 mg/day of magnesium to 46 elderly participants experiencing primary insomnia over an 8-week period, with outcomes including increased sleep duration and efficiency, as well as reduced ISI scores and sleep onset latency. Additionally, it improved objective indicators of insomnia, such as the concentrations of serum renin, melatonin, and serum cortisol. Three randomized controlled trials involving 151 elderly participants across three countries compared the effects of oral magnesium with placebo. A systematic review and meta-analysis highlighted that, compared to placebo, magnesium supplementation reduced sleep onset latency by 17.36 min (P=0.0006) and extended total sleep time by 16.06 min, supporting the use of oral magnesium supplements (up to three times a day, with each dose less than 1 g) for treating insomnia symptoms. Rondanelli et al found that, compared to placebo capsules, administering a formulation containing melatonin, magnesium, and zinc to 43 elderly subjects with primary insomnia, one hour before bedtime over an 8-week period, enhanced sleep quality and increased the total sleep time as measured by wearable arm sensors. More recently, preliminary research by Honiak et al also concluded that magnesium supplementation could serve as a valuable alternative therapy for patients with insomnia. In the treatment of insomnia, as an adjuvant therapy, magnesium not only acts as a natural NMDA antagonist and GABA agonist but also has a relaxing effect. Magnesium deficiency can cause muscle cramps, leading to poor sleep. Moreover, magnesium can increase melatonin levels, aiding in the maintenance of a normal biological clock and the alleviation of insomnia symptoms. Another study further indicated that magnesium may alleviate insomnia associated with restless legs syndrome. Additionally, the serotonergic system represents another pathway potentially modulated by magnesium. Magnesium in Idiopathic Hypersomnia and Narcolepsy Idiopathic hypersomnia and narcolepsy are rare chronic sleep disorders that can impair patients’ cognitive function, social functioning, and health-related quality of life. Their primary characteristic is excessive daytime sleepiness, with many narcolepsy patients also experiencing cataplexy. In addition, narcolepsy is associated with nighttime sleep disturbances, hypnagogic and hypnopompic hallucinations, as well as sleep paralysis. For idiopathic
Magnesium – Supplementation could be GREAT for Cardiac Diseases in Indians
Heavy Burden of HEART Diseases in India The noncommunicable diseases commonly include cardiovascular disease (CVD), various cancers, chronic respiratory illnesses, diabetes, and so on which are estimated to account for around 60% of all deaths. CVDs such as ischemic heart disease and cerebrovascular such as stroke account for 17.7 million deaths and are the leading cause. In accordance with the World Health Organization, India accounts for one-fifth of these deaths worldwide especially in younger population. The results of Global Burden of Disease study state age-standardized CVD death rate of 272 per 100000 population in India which is much higher than that of global average of 235. CVDs strike Indians a decade earlier than the western population. For us Indians, particular causes of concern in CVD are early age of onset, rapid progression and high mortality rate. Indians are known to have the highest coronary artery disease (CAD) rates, and the conventional risk factors fail to explain this increased risk. In India in 2016, CVDs contributed to 28·1% of total deaths and 14·1% of total disability-adjusted life years (DALYs) compared with 15·2% and 6·9%, respectively in 1990. Within India, the rates of CVD vary markedly with highest in states of Kerala, Punjab and Tamil Nadu. Moreover, these states also have the highest prevalence of raised cholesterol levels and blood pressure. At present, India has the highest burden of acute coronary syndrome and ST-elevation myocardial infarction (MI). Another significant problem in India, among other CVD’s, is that of hypertensive heart disease, with 261,694 deaths in 2013 (an increase of 138% in comparison with 1990). Rheumatic heart disease remains in epidemic proportions in India with an estimated prevalence of 1.5-2 per 1000 individuals. Migrant Asian Indians have a 3-time higher prevalence of CAD than the native population. Indians are liable to get hospitalized 2–4 times more frequently for complications of CAD, in comparison with other ethnic groups, and admission rates are 5–10 times higher for populations younger than 40 years. The prevalence of CAD in Indians living in India is 21.4% for diabetics and 11% for nondiabetics. The prevalence of CAD in rural parts of country is nearly half than that in urban population. Magnesium – How Magnesium Supplementation May SIGNIFICANTLY Help in CVDs Magnesium is a plentiful micronutrient and cation, and it activates enzymes, aids in the synthesis of energy, and controls the levels of calcium and associated biomarkers, among other vital functions in the body. Low magnesium levels have been linked to CVD through a variety of physiological processes, including high blood sugar levels, chronic inflammation, hypertension, abnormal tone of the vessels, and circulation to the peripheral tissues. In various settings, total magnesium in the serum has long been used to evaluate magnesium levels. In multiple studies, low levels of magnesium have been linked to a higher risk of various health problems, such as a greater risk of diabetes, hypertension, and CVD. Given the high prevalence of CVDs and their significant public health impact, investigating the link between magnesium deficiency and cardiovascular risk becomes imperative. Role of Magnesium in cardiovascular health Magnesium improves the function of the cardiovascular system by acting on membrane ion flow pumps, encouraging endothelium-dependent blood vessel dilatation, reducing blood pressure, reducing inflammation, and boosting insulin and glucose breakdown. In addition, magnesium contains antiplatelet and anticoagulant characteristics, is a natural inhibitor of calcium, and is a necessary cofactor in cellular oxidation reactions. Magnesium’s Role in Modulating Ionic Channels Certain ionic channels, including calcium, potassium, and sodium, are controlled in part by magnesium. Magnesium regulates cardiac responsiveness and the length of action potentials by decreasing the fast influx element of the delayed rectifier potassium channel. Magnesium influx influences the elongation of QRS and PR duration on ECG and also slows atrioventricular node conductivity. Magnesium inhibits coronary vessel spasm, plays a critical function in regulating vascular muscle tone and, consequently, systemic arterial blood pressure, and provides protection against stimulated activity through its antagonistic impact on two calcium channels, transient type (T-type) and long-lasting type (L-type). Magnesium is also essential for the exchange of potassium for protons as well as for preventing potassium loss. In addition to competing for the same binding sites as calcium, magnesium might restrict the extent of the infarct by minimizing coronary vessel contractions, lowering damage from oxidation after myocardial infarction, and enhancing endothelial-dependent dilatation of vessels through the production of nitrous oxide during myocardial ischemia. Magnesium’s Role in Metabolic Regulation By lowering the likelihood of metabolic syndrome and type 2 diabetes mellitus, magnesium supplementation appears to have positive benefits on cardiovascular health. The glucose transporter protein 4 is regulated by this ion, which improves insulin responsiveness and increases both insulin and glucose breakdown. Magnesium has been shown to control post=receptor signaling via insulin, mediate insulin release from the pancreas, and function as a second responder for transmitting insulin-mediated signals. Magnesium’s Role in Regulating Inflammatory Reactions Magnesium exhibits antioxidant properties by neutralizing free radicals of oxygen and reduces inflammation by regulating the expression of nuclear factor kappa B. In hypomagnesemia, the inflammation that occurs also affects the balance of lipids by lipid peroxidation, which leads to dyslipidemia by raising lipids rich in triglycerides, boosting plasma levels of a protein called apolipoprotein B, and lowering the concentrations of high-density lipoprotein cholesterol (HDL-C). Magnesium’s Role in Hemostasis and Coagulation Magnesium can prevent the accumulation of platelets by competing with the ions of calcium for particular places in the glycoprotein (Gp) IIb subunit, changing the receptor’s configuration, and preventing interactions between Gp IIb-IIIa and fibrinogen. Additionally, magnesium can decrease the activation of platelets by preventing the synthesis of factors that stimulate platelets, like thromboxane A2, and by promoting the breakdown of factors that inhibit platelets, like prostacyclin. Clinical Evidence – Magnesium Supplementation and Cardiac Arrhythmias A study was conducted by Raghu et al. on 55 participants with a cardiac response rate of more than 120 beats/minute and atrial fibrillation. Of them, 75% received treatment with magnesium sulfate (MgSO4) and 25% received a placebo. In addition to conventional therapy, 2.5 grams of intravenous MgSO4 was given, and it
Thiamine Vit B1 – Why You MUST Supplement
What is thiamine? Thiamine (aka vitamin B1) is an essential water-soluble vitamin that plays a crucial role in how cells make energy. It is also very important for how nerves send messages throughout the body, and how the brain makes specific neurochemicals. It is a key cofactor for enzymes involved in converting carbohydrates/fats/proteins into ATP, the body’s primary energy source. Thiamine is especially needed for production of the neurotransmitter acetylcholine. It is therefore extremely important for the autonomic nervous system, and maintaining the balance between sympathetic and parasympathetic modes Sources of Thiamine – Vit B1 It is found in a variety of foods in low amounts: meats, organs, legumes, whole grains. From a conventional standpoint, a severe deficiency is known to affect the brain, heart, peripheral nerves, and gut. However, a mild deficiency can lead to a wide variety of NON SPECIFIC symptoms, which vary from person to person: Fatigue, brain fog, nerve pain, muscle pain, insomnia, anxiety, restlessness, autonomic nervous system problems/dysautonomia (blood pressure imbalances, vertigo, circulation problems, heart rate problems, body temperature dysregulation), SIBO, stomach acidity imbalances, constipation, sometimes diarrhea, intestinal permeability and any number of function gut disorders. What causes Thiamine / Vit B1 deficiency There are many potential causes. Thiamine status depends on carbohydrate intake, meaning the more carbs/sugar someone consumes, the greater demand for thiamine. High intake of refined carbohydrate/refined foods – Alcohol destroys thiamine – Tannins (not caffeine) in tea/coffee inactivate thiamine Medications: Metronidazole/flagyl, metformin, diuretics, omeprazole – Sulfites destroy thiamine Chronic gut conditions which involve nutrient malabsorption/gut inflammation Any state of prolonged physical stress (excessive exercise, critical illness, hyperthyroid, etc) In short, there are numerous things which can lead to/trigger a deficiency. A classical deficiency can be fairly straightforward to treat, but can take several months to manifest (depending on severity of the deficiency). However, there are also many individuals who don’t display the risk factors, but respond to high-doses of thiamine. What is a “Functional” or “Localized” Thiamine / Vit B1 deficiency? Localized or Functional Deficiency – This occurs in people who have normal systemic levels of thiamine in their body. However, certain regions of the body can experience a localized deficiency. For example, in neurodegenerative diseases, the research suggests localized “deficiency” in the brain. Without going into the mechanistic details, this can occur for various reasons, and can either be due to problems with transporting thiamine into the brain and into the cells. Or it can be related to problems with enzymes in cells which use thiamine. It can occur in the heart, the brain, the gut, etc. In this scenario, taking normal doses of thiamine is not enough. For people to see improvements in their condition, they generally require anywhere from 300-2000x the RDA (300mg to 2000mg, depending on the form of thiamine used). Here is where blood testing/functional testing becomes useless, because it doesn’t measure what is going on at the organ/cell level of the affected area. Different forms of Thiamine / Vit B1 Thiamine HCL/mononitrate – Cheap but not well absorbed. Can be useful in high doses above 500mg Benfotiamine – well absorbed and gets into brain, good for peripheral neuropathy, diabetes, body pain, fatigue, Alzheimer’s’. Usually dosed between 150-2100mg TTFD (thiamine tetrahydrofurfuryl disulfide) – well absorbed and gets into brain – best for gut issues of any kind, POTS/dysautonomia and mood issues. Also good for fatigue, and neuropathy. Contains sulfur, so can trigger unwanted symptoms in some people. Usually dosed between 100-500mg Basic Thiamine / Vit B1 Supplementation Protocol Start low and go slow with whichever form of B1 (think 10-50mg). Take B complex, magnesium and potassium as well. Gradually increase dose of thiamine over the space of days/weeks. Watch for changes in symptoms. As increasing the dose, symptoms can get temporarily worse (called the paradoxical effect). If symptoms worsen, stay at current dose until they return to baseline. – When symptoms return to baseline, work on increasing dose again.
Vitamins – Critically Essential for Optimal Brain Function and Health
Your brain is the most energy-hungry organ in the body. Every thought, movement, and emotion depends on a continuous supply of nutrients that maintain energy production, neuronal structure, and neurotransmitter balance. Vitamins and bioactive compounds do not just support brain health in a general sense; they perform specific biochemical roles in how neurons generate, transmit, and respond to signals. Homocysteine Metabolism Vitamins B6, B9 (folate), B12, riboflavin, choline, and niacin (B3) regulate homocysteine, an amino acid that can damage blood vessels and neurons when elevated. Adequate folate and B12 reduce homocysteine levels, supporting long-term cognitive function. Example: Supplementing B12 and folate in older adults with elevated homocysteine has been shown to slow brain atrophy and improve memory performance. Energy Metabolism The brain needs a constant ATP supply to sustain signaling and plasticity. B vitamins, lipoic acid, CoQ10, iron, and manganese act as cofactors in mitochondrial energy production. A deficiency in thiamine (B1) or riboflavin (B2) impairs energy metabolism and can contribute to fatigue, poor focus, or cognitive fog. Example: Patients with thiamine deficiency often experience reversible confusion and energy loss once repleted with B1. Neurotransmitter Synthesis and Binding Vitamin B6 is required to convert amino acids into neurotransmitters such as serotonin, dopamine, and GABA. Low B6 disrupts these conversions and weakens mood regulation. Example: B6 supplementation in individuals with low serotonin production improves emotional stability and stress resilience by restoring neurotransmitter balance. Nerve Signal Transmission Efficient signal propagation relies on nutrients that maintain myelin integrity and axonal firing. DHA, folate (B9), B12, thiamine, and iron are all critical for this process. Example: Low B12 can lead to nerve demyelination and neuropathy, while DHA from omega-3s improves communication speed between neurons. Membrane Integrity Neuronal membranes are rich in fats that are easily oxidized. DHA, EPA, vitamins C and E, and polyphenols protect and stabilize these membranes. Example: Vitamin E helps prevent oxidation of brain fats, and vitamin C regenerates vitamin E, maintaining optimal membrane fluidity and receptor function. Neuron Growth and Development Vitamin D, polyphenols, and flavonoids influence neuronal growth, repair, and plasticity. Example: Vitamin D receptors in the hippocampus regulate genes tied to memory formation, while berry polyphenols increase brain-derived neurotrophic factor (BDNF), promoting neurogenesis. Blood Flow and Oxygen Delivery Polyphenols and flavonoids enhance vascular function and cerebral blood flow, ensuring that neurons receive adequate oxygen and nutrients. Example: Cocoa flavanols and blueberry extracts have been shown to increase brain blood flow and improve cognitive performance in both young and older adults. Brain performance relies on more than calories and oxygen. Micronutrients provide the molecular infrastructure for energy production, neurotransmission, protection, and plasticity. B vitamins fuel mitochondria, DHA and antioxidants preserve neuronal membranes, and polyphenols and vitamin D enhance repair and blood flow. The right micronutrients do not just protect the brain; they help it adapt, learn, and thrive.
Vitamins and Minerals – Which Organs Store these
Where vitamins and minerals are stored in the body Vitamins and minerals use different storage strategies. Some are stockpiled in organs and tissues, while others are used immediately and must be replenished often. Storage pattern explains why some deficiencies appear quickly and why a few nutrients can accumulate to toxic levels if overconsumed. Water-soluble vitamins (B-complex, vitamin C) Mostly circulate in blood and are not stored in large amounts. Excess is lost in urine, so steady intake matters. Vitamin B12 is the notable exception and is stored in the liver for years. Example: within a few weeks with little vitamin C can already cause fatigue and gum irritation, while low B12 may not show up for months because liver stores buffer intake. Example: intense sweating or diuretics can raise B-vitamin needs since these B Vitamins dissolve and leave the body with fluids. Fat-soluble vitamins (A, D, E, K) Absorbed with dietary fat and stored in liver, adipose tissue, and to a lesser extent skin. Deficiency develops slowly, and excess intake can accumulate. Example: vitamin D is stored in liver and fat and can help maintain status through winter when sunlight is low. Example: chronic high vitamin A intake from supplements can build up in the liver and cause headaches or skin peeling. Major minerals (calcium, magnesium, phosphorus, potassium, sodium, chloride, sulfur) Stored mainly in bone, muscle, and extracellular fluids. They maintain structure and electrical balance. Example: about 99 percent of calcium is stored in bone; low dietary calcium draws from bone reserves over time, weakening bone density. Example: magnesium is stored in bone and muscle; heavy sweating or stress can deplete it and trigger muscle cramps or irregular heartbeat. Example: sodium and chloride are held in extracellular fluids; high salt intake increases extracellular volume and can raise blood pressure in salt-sensitive people. Trace minerals (iron, zinc, copper, selenium, iodine, manganese, chromium, molybdenum, fluoride) Required in small amounts with specific storage sites. Example: iron is stored as ferritin in liver, spleen, and bone marrow; low ferritin reduces red blood cell production and causes fatigue. Example: iodine concentrates in the thyroid gland to make thyroid hormones; low iodine intake slows metabolism and can enlarge the thyroid. Example: zinc is distributed in skin, pancreas, and brain; low zinc impairs wound healing and blunts taste and smell. Choline and other water-soluble nutrients Choline is stored in the liver and incorporated into phospholipids and acetylcholine. Example: inadequate choline raises risk for fatty liver and can affect memory because the body cannot synthesize enough to cover needs in many people. Water-soluble vitamins are used quickly and need regular intake. Fat-soluble vitamins and many minerals can be stored for longer periods, which delays deficiency but increases the risk of buildup with excessive supplementation. The liver, bone, muscle, fat, and thyroid serve as the body’s nutrient vaults, releasing or storing what the brain and tissues need in real time.