Biotin & Triglycerides - why perhaps Fish Oil and Niacin may actually help a little in Autism & Schizophrenia

Far back in this blog, I wrote a post about fish oil.  Omega 3 oils are definitely good for your general health, but do they help with autism?  They are also claimed to help with ADHD and improve your NT child’s cognitive performance.

On critical review of the evidence, it seemed that the benefit was far from conclusive.  There was one very positive study, that neither the authors nor anyone else could repeat.

The following review of the literature by the University of Maryland show that, as with autism, studies on fish oil in depression, ADHD, bipolar and schizophrenia show conflicting results.

Omega-3 fatty acids

Some of the “cognitive enhancing” fish oil products are extremely expensive and I showed that regular fish consumption was far cheaper and likely to be as effective.

There is an issue of just how big an effect you are looking for.  We can all imagine tiny effects, but you really want an effect that everyone else notices.

Monty, aged 11 with ASD, eats lots of fish, mainly because he loves it.  He is not at all put off by those little bones.

The effect of fish oil on Monty was not noticeable.

Biotin

A recent post contained a study from Greece, where they found a remarkably high proportion of kids with ASD with a biotin deficiency.  This had not shown up on the standard test, because the standard test is strangely not for biotin at all; it tests for biotinidase, a related enzyme.

Identifying a biotin deficiency is not easy, blood tests are not helpful and you have to look at certain compounds found in urine.  As a result your local laboratory may not offer a useful test for biotin.

Since supplementation with pharmacological doses of biotin is known to be harmless, the practical way forward is to try it.

In the midst of looking at the relative effect of different primary antioxidants, I was substituting one thiol antioxidant (ALA) for another (NAC) to see if there was any obvious difference.  I could give lots of reasons, with scientific papers to back them up, as to why 0.6g of ALA plus 1.8g of NAC might be “better” than 2.4g of NAC, but it is not.  If anything, it might be worse.

Then I tried Carnosine in combination with NAC and again I could see absolutely no effect.

Then I decided to go back to my original NAC regime and add the biotin that had been on the shelf since Christmas. Very surprisingly, the effect that I thought might show up with ALA, showed up with biotin.  

It was not a huge effect, but a small step forward, that Monty’s assistant at school also noticed.  He was more calm and altogether more "normal". 

Does this mean Monty has a biotin deficiency?  It is of course possible.  In the Greek study 4% of the kids were thought to have such a deficiency, far more than expected, and most did respond, in varying degrees, to biotin supplements.  Unfortunately they only gave the biotin to the 4%; I would like to know what would have happened to the remaining 96%.

Biotin lowers Triglycerides and Elevated Triglycerides are associated with Mood Disorders   

Biotin is a B vitamin, but very little is actually known about it.

Then I found the link I was looking for.

Biotin does not lower cholesterol, but it does reduce (in a big way) your Triglycerides.

Several studies have shown that elevated Triglycerides are associated with all kinds of disorders: bipolar, depression and schizophrenia.  These studies suggested a causal link between the mood disorder and the elevated triglyerides.

Other Effects on Mood

          Besides depression, high levels of triglycerides are also correlated with other affective disorders including bipolar disorder (manic depression), schizoaffective disorders, aggression and hostility. In fact, the poor nutritional status of many depressed persons, who often have diets high in fats, can be improved to lessen the depression, according to Charles Glueck, MD, medical director of the Cholesterol Center of Jewish Hospital in Cincinnati.

"We have shown that in patients with high triglycerides who were in a depressive state, the more you lower the triglycerides, the more you alleviate the depression," Glueck wrote in a 1993 article in Biological Psychiatry.

According to the U.S. Centers for Disease Control and Prevention (CDC), most Americans aren't aware of the role triglycerides play in physical and mental health. A five-year study of more than 5,000 Americans found that 33 percent of them had borderline high triglyceride levels.

Improvement in symptoms of depression and in an index of life stressors accompany treatment of severe hypertriglyceridemia.

In 14 men and nine women referred because of severe primary hypertriglyceridemia, our specific aim in a 54-week single-blind treatment (Rx) period was to determine whether triglyceride (TG) lowering with a Type V diet and Lopid would lead to improvement in symptoms of depression, improvement in an index of life stressors, change in locus of control index, and improved cognition, as serially tested by Beck (BDI), Hassles (HAS) and HAS intensity indices, Locus of Control index, and the Folstein Mini-Mental status exam. On Rx, median TG fell 47%, total cholesterol (TC) fell 15%, and HDLC rose 19% (all p < or = 0.001). BDI fell at all nine Rx visits (p < or = 0.001), a major reduction in a test of depressive symptoms. The HAS score also fell at all nine visits (p < or = 0.05 - < or = 0.001). Comparing pre-Rx baseline BDI vs BDI at 30 and 54 weeks on Rx, there was a major shift towards absence or amelioration of depressive symptoms (chi 2= 5.9, p = 0.016). On Rx, the greater the percent reduction in TG, the greater the percent fall in BDI (r = 0.47, p < or = 0.05); the greater the percent reduction in TC, the greater the percent fall in HAS (r = 0.41, p < or = 0.05). Improvement in the BDI and HAS accompanied treatment of severe hypertriglyceridemia, possibly by virtue of improved cerebral perfusion and oxygenation. There may be a reversible causal relationship between high TG and symptoms of depression.

Mood symptoms and serum lipids in acute phase of bipolar disorder inTaiwan.

 

Abstract

Serum lipids have been found to play important roles in the pathophysiology of mood disorders. The aim of the present study was therefore to investigate the relationship between symptom dimensions and serum cholesterol and triglyceride levels, and to explore correlates of lipid levels during acute mood episodes of bipolar I disorder in Taiwan. Measurements were taken of the serum cholesterol and triglyceride levels in patients with bipolar I disorder hospitalized for acute mood episodes (68 manic, eight depressive, and six mixed). The relationships between serum lipids levels and various clinical variables were examined. The mean serum levels of cholesterol (4.54 mmol/L) and triglycerides (1.16 mmol/L) of sampled patients were comparable to those of the general population in the same age segment. Severe depressive symptoms and comorbid atopic diseases were associated with higher serum cholesterol levels. A negative association was noted between serum triglyceride levels and overall psychiatric symptoms. Compared with previous studies on Western populations, racial differences may exist in lipids profiles of bipolar disorder patients during acute mood episodes. Increased serum cholesterol levels may have greater relevance to immunomodulatory system and depressive symptoms, in comparison with manic symptoms.

Biotin supplementation reduces plasma triacylglycerol and VLDL in type 2 diabetic patients and in non-diabetic subjects with hypertriglyceridemia.

Abstract

Biotin is a water-soluble vitamin that acts as a prosthetic group of carboxylases. Besides its role as carboxylase prosthetic group, biotin regulates gene expression and has a wide repertoire of effects on systemic processes. The vitamin regulates genes that are critical in the regulation of intermediary metabolism. Several studies have reported a relationship between biotin and blood lipids. In the present work we investigated the effect of biotin administration on the concentration of plasma lipids, as well as glucose and insulin in type 2 diabetic and nondiabetic subjects. Eighteen diabetic and 15 nondiabetic subjects aged 30-65 were randomized into two groups and received either 61.4 micromol/day of biotin or placebo for 28 days. Plasma samples obtained at baseline and after treatment were analyzed for total triglyceride, cholesterol, very low density lipoprotein (VLDL), glucose and insulin. We found that the vitamin significantly reduced (P=0.005) plasma triacylglycerol and VLDL concentrations. Biotin produced the following changes (mean of absolute differences between 0 and 28 day treatment+/-S.E.M.): a) triacylglycerol -0.55+/-0.2 in the diabetic group and -0.92+/-0.36 in the nondiabetic group; b) VLDL: -0.11+/-0.04 in the diabetic group and -0.18+/-0.07 in the nondiabetic group. Biotin treatment had no significant effects on cholesterol, glucose and insulin in either the diabetic or nondiabetic subjects. We conclude that pharmacological doses of biotin decrease hypertriglyceridemia. The triglyceride-lowering effect of biotin suggests that biotin could be used in the treatment of hypertriglyceridemia.

The hypotriglyceridemic effect of biotin supplementation involves increased levels of cGMP and AMPK activation

Abstract

In addition to its role as a carboxylase cofactor, biotin modifies gene expression and has manifold effects on systemic processes. Several studies have shown that biotin supplementation reduces hypertriglyceridemia. We have previously reported that this effect is related to decreased expression of lipogenic genes. In the present work, we analyzed signaling pathways and posttranscriptional mechanisms involved in the hypotriglyceridemic effects of biotin. Male BALB/cAnN Hsd mice were fed a control or a biotin-supplemented diet (1.76 or 97.7 mg of free biotin/kg diet, respectively for 8 weeks after weaning. The abundance of mature sterol regulatory element-binding protein (SREBP-1c), fatty-acid synthase (FAS), total acetyl-CoA carboxylase-1 (ACC-1) and its phosphorylated form, and AMP-activated protein kinase (AMPK) were evaluated in the liver. We also determined the serum triglyceride concentrations and the hepatic levels of triglycerides and cyclic GMP (cGMP). Compared to the control group, biotin-supplemented mice had lower serum and hepatic triglyceride concentrations. Biotin supplementation increased the levels of cGMP and the phosphorylated forms of AMPK and ACC-1 and decreased the abundance of the mature form of SREBP-1c and FAS. These data provide evidence that the mechanisms by which biotin supplementation reduces lipogenesis involve increased cGMP content and AMPK activation. In turn, these changes lead to augmented ACC-1 phosphorylation and decreased expression of both the mature form of SREBP-1c and FAS. Our results demonstrate for the first time that AMPK is involved in the effects of biotin supplementation and offer new insights into the mechanisms of biotin-mediated hypotriglyceridemic effects.

Triglycerides are also elevated in autism:-

Alterations in lipid profile of autistic boys: a case control study.

Abstract

We hypothesize that autism is associated with alterations in the plasma lipid profile and that some lipid fractions in autistic boys may be significantly different than those of healthy boys. A matched case control study was conducted with 29 autistic boys (mean age, 10.1 +/- 1.3 years) recruited from a school for disabled children and 29 comparable healthy boys from a neighboring elementary school in South Korea. Fasting plasma total cholesterol (T-Chol), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), the LDL/HDL ratio, and 1-day food intakes were measured. Multiple regression analyses were performed to assess the association between autism and various lipid fractions. The mean TG level (102.4 +/- 52.4 vs 70.6 +/- 36.3; P = .01) was significantly higher, whereas the mean HDL-C level (48.8 +/- 11.9 vs 60.5 +/- 10.9 mg/dL; P = .003) was significantly lower in cases as compared to controls. There was no significant difference in T-Chol and LDL-C levels between cases and controls. The LDL/HDL ratio was significantly higher in cases as compared to controls. Multiple regression analyses indicated that autism was significantly associated with plasma TG (beta = 31.7 +/- 11.9; P = .01), HDL (beta = -11.6 +/- 2.1; P = .0003), and the LDL/HDL ratio (beta = 0.40 +/- 0.18; P = .04). There was a significant interaction between autism and TG level in relation to plasma HDL level (P = .02). Fifty-three percent of variation in the plasma HDL was explained by autism, plasma TG, LDL/HDL ratio, and the interaction between autism and plasma TG level. These results indicate the presence of dyslipidemia in boys with autism and suggest a possibility that dyslipidemia might be a marker of association between lipid metabolism and autism.

Omega-3 Oil and Niacin in Schizophrenia

Like Autism, Schizophrenia is another observational diagnosis, with many different underlying genetic and environmental causes.  I keep referring to it as adult-onset autism.  It is also characterized by oxidative stress.

I found it interesting that two very widely used therapies for schizophrenia are omega-3 fish oil and high doses of niacin.  2 g a day of NAC is another common therapy in schizophrenia.

The clinical trials of omega-3 oil in schizophrenia, are just like the ones in autism, far from conclusive.  Yet people with schizophrenia continue to buy the expensive EPA fish oils, just like many parents of children with autism.

Another very popular treatment is Niacin.

Niacin does many things but these include increasing your HDL (good) cholesterol, reduce LDL (bad) cholesterol and, importantly, can reduce triglycerides by up to 50%.

Management of Hypertriglyceridemia

Niacin in Anxiety

Supplemental Niacinamide Mitigates Anxiety Symptoms: Three Case Reports

Niacin in autism

People do use high dose niacin and niacinamide in autism, but in general niacin levels are totally normal in people with autism, according to this study:-

Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity

For the vitamins, the only significant difference was a 20% lower biotin (p < 0.001) in the children with autism. There were possibly significant (p < 0.05) lower levels of vitamin B5, vitamin E, and total carotenoids. Vitamin C was possibly slightly higher in the children with autism. Vitamin B6 (measured as the active form, P5P, in the RBC) had an unusually broad distribution in children with autism compared to controls (see Figure ​Figure1),1), with the levels in the children with autism having 3 times the standard deviation of the neurotypical children.

Niacin was very similar in the autism group (7.00 μg/l and the control group (7.07 μg/l)

Other interesting findings highlighted the usual metabolic differences:-

·        ATP, NADH, and NAHPH were significantly different between the autism and neurotypical groups

·        Sulfation, methylation, glutathione, and oxidative stress biomarkers which were significantly different between the autism and neurotypical groups

·        Amino Acids which were significantly different between the autism and neurotypical groups, rescaled to the average neurotypical value

Peter Triglyceride Hypothesis in Autism & Schizophrenia

Elevated triglycerides in autism/schizophrenia may contribute to behavioral/mood problems.  The lipid contribution to the dysfunction may be correlated to elevation of triglycerides.  In other words triglycerides aggravate the existing disorder.

Some CAM treatments currently used in autism/schizophrenia, including high dose niacin, high dose biotin and high dose omega 3 oils may be effective due to their ability to lower triglycerides.

Biotin may be the safest, cheapest and most effective option to reduce triglycerides and improve mood/behavior.

The underlying cause of lipid dysfunction in autism/schizophrenia is the ongoing oxidative stress.

Fish oil is claimed to be good for your heart, but it has been shown not to affect cholesterol levels.  In some studies it did lower triglycerides.  In some countries doctors prescribe omega-3 oil to patients with stubbornly high triglycerides.  Perhaps they should read the research and try biotin?

  

Other functions of biotin

Biotin does have other more complex functions and the triglycerides may, so to speak, be a red herring.

Regulation of gene expression by biotin (review).

Abstract

In mammals, biotin serves as coenzyme for four carboxylases, which play essential roles in the metabolism of glucose, amino acids, and fatty acids. Biotin deficiency causes decreased rates of cell proliferation, impaired immune function, and abnormal fetal development. Evidence is accumulating that biotin also plays an important role in regulating gene expression, mediating some of the effects of biotin in cell biology and fetal development. DNA microarray studies and other gene expression studies have suggested that biotin affects transcription of genes encoding cytokines and their receptors, oncogenes, genes involved in glucose metabolism, and genes that play a role in cellular biotin homeostasis. In addition, evidence has been provided that biotin affects expression of the asialoglycoprotein receptor and propionyl-CoA carboxylase at the post-transcriptional level. Various pathways have been identified by which biotin might affect gene expression: activation of soluble guanylate cyclase by biotinyl-AMP, nuclear translocation of NF-kappaB (in response to biotin deficiency), and remodeling of chromatin by biotinylation of histones. Some biotin metabolites that cannot serve as coenzymes for carboxylases can mimic biotin with regard to its effects on gene expression. This observation suggests that biotin metabolites that have been considered "metabolic waste" in previous studies might have biotin-like activities. These new insights into biotin-dependent gene expression are likely to lead to a better understanding of roles for biotin in cell biology and fetal development.

It does appear that biotin is more important than generally appreciated. 

Conclusion

In earlier posts I highlighted that elevated cholesterol is a bio-marker for inflammation.  In a large sub-group in autism, cholesterol is elevated.

In today’s post we looked at  a different type of lipid, triglycerides, they have a different role to cholesterol.  Not surprisingly the lipid profile is dysfunction, since it is closely linked to oxidative stress, which appears to be at the root of many problems in autism.

It is extremely easy and inexpensive to check your lipid profile (LDL, HDL and triglycerides); if elevated, there are safe established ways to bring things back to “normal”.

Parents seeing a small positive effect with their fish oil supplements might consider saving a lot of money and seeing if an extremely inexpensive biotin (5mg) supplement has an equal or greater effect.  The cost of biotin would be $2 a month.  The cost of fish oil with anything like the concentration used in the more effective trials (0.84g EPA and 0.7g DHA) will cost around $50 a month and may not lower triglycerides by as much as the cheap biotin.

By measuring the lipid profile before and after, you will be able to determine for yourself the relative merits.

Niacin also has been shown to improve mood/anxiety.  It is used by people with autism and schizophrenia.  Niacin is also extremely effective at reducing triglycerides.  High doses of Niacin can be accompanied by side effects and so use is discouraged.

Biotin levels do seem to be slightly low in autism.  Effective methods of accurately diagnosing deficiency are disputed.  Biotin is very effective at reducing triglycerides.

Elevated triglycerides have been associated with mood disorders and depression.

It seems plausible that the benefits from Omega-3 , niacin and biotin stem from their effectiveness in reducing triglycerides.

Biotin would seem to be a very cost effective and safe way to achieve this, without the side effects of niacin.  

Biotin also appears to have other key functions, including transcription of cytokine genes. Over expression of pro-inflammatory cytokines is a common feature of autism.