Summary of fortune article with respect to Alzheimer’s disease and L-serine as a possible treatment. You can read the full article here.

An article was published in Fortune magazine in February of 2019 concerning the possible prevention of Tangle diseases by the daily dosing of L-serine- a naturally occurring Amino acid used by the body to prevent the misfolding of proteins – which protects neurons in the brain. 

The research was done by DR. Paul Cox, PHD and the Brain Chemistry Labs in Jackson Hole, Wyoming. They have published research on their findings and have concentrated their efforts on L-serine which they believe could significantly delay the onset of Alzheimer’s and the progress of its symptoms. The FDA has previously approved the use of L-serine as a safe dietary supplement, and doctors sometime proscribe it for chronic fatigue syndrome. The Cox team believes L-serine may play a neuroprotective role.

For Cox, the most powerful illustration of L-serine potential is a 2016 study he and the University of Miami’s Mash oversaw on St. Kitts in the British Virgin Islands. A team at an animal research lab there fed bananas loaded with BMAA -identified to cause tangles, L-serine, or a combination of both to vervet monkeys who have a gene that is thought to increase the risk of Alzheimer’s in humans.( The control Group got bananas with rice flour). Monkeys given BMAA showed both plaques and tangles common to Alzheimer’s patients. But those given an accompanying dose of L-serine had 80% to 90% fewer tangles in their brain tissue, the study found. The results astounded Mash and Cox, so they repeated the effort with another 140 vervets and got comparable results. Their findings were published in the PROCEEDINGS of the ROYAL SOCIETY.

Early in 2017, Cox published the results of a six-month clinical trial of L-serine given at varying doses to ALS patients. The phase I trial, conducted by independent labs in San Francisco and Phoenix, showed once again that L-serine is safe for humans. One piece of data stood out which was published in a respected ALS journal. The four patients who received the highest doses of L-serine (30 grams a day) saw the progress of their symptoms, as measured on a widely used scale known as ALSFRS-R, slow by 85%. The number of patients, in this case, was too small for the finding to reach statistical significance, but if further clinical trials replicate anything close to that percentage, L-serine would slow the progress of symptoms far more than any existing drug, potentially buying patients years of life. (the average ALS patient dies 2.5 years after diagnosis).

Cox and the brain chemistry labs are conducting Phase II trials currently at Dartmouth medical school and in North Carolina. They are expecting results sometime this year that will support the pervious trials.

In the absence of a cure, the pool of Alzheimer’s patients will soar: while 47 million people worldwide live with Alzheimer’s today, 141 million may have the disease in 2050, according to the Alzheimer’s association. In the US alone, the financial cost of caring for today's 5.7 million patients is a staggering annual $277 billion. By mid-century, Americans may spend $1.1 trillion annually on Alzheimer’s, a crippling blow to a reeling health care system.

The FDA’s Role in the Supplement Industry

• The FDA does not approve any vitamin or supplement
• The FDA treats nutritional supplements as a subset of food products rather than drugs
• Because supplements are not treated like pharmaceutical drugs, they cannot make claims related to disease.

Sometimes on vitamin or supplement websites you’ll see the disclaimer: “These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.”

To the untrained eye, this statement might look a little suspect. But it’s actually perfectly normal and required by the FDA in certain instances. So what exactly is the FDA’s role in the supplement industry, and what do those two little sentences even mean? Let’s dive in.

First things first: what is the FDA?

The FDA or the U.S. Food and Drug Administration is a federal agency responsible for regulating products that impact public health, such as food products, pharmaceutical drugs, medical devices, cosmetics, and even tobacco products. The FDA plays an important part in ensuring the safety of the products we use every day, but is not a source of approval for every industry that it oversees. More on that later.

What does the FDA have to do with supplements?

In the dietary supplement industry, the FDA acts as an enforcement and regulatory agency. This includes defining and enforcing what supplement companies can claim about their products.

To ensure public safety, the FDA has defined Good Manufacturing Practices (GMPs) that it enforces through inspections, and has the authority to prosecute, seize and remove dangerous products from the marketplace. The FDA can also determine if a product is Generally Recognized As Safe (GRAS) after reviewing evidence.

How were the FDA’s rules and regulations determined?

Up until the late 1930s, the food and drug industry was widely unregulated, except for a piece of legislation from 1906 that prohibited misbranded and adulterated food and drugs.

In the early part of the 20th century, many people died from using consumer products that were not safe for human consumption--sparking public outrage and political pressure. In 1937, the issue reached a fever point when an untested medicine killed hundreds of patients, including many children, shortly after its release onto the market. In response, congress passed the Food, Drug, and Cosmetic Act in 1938.

Under the rules of the FD&C Act, foods are treated separately from drugs. Drugs, which are defined as products used for medical purposes, come under stricter regulation. Foods, defined as products used for nutritional purposes, have fewer restrictions. This line in the sand--medical (drug) vs. nutritional (food)--is important because under the FD&C Act, vitamins and other supplements are treated as a subset of food products rather than drug products.

What’s the difference between a drug and a supplement?

According to the FDA, drugs are for treating, preventing, mitigating, diagnosing or curing diseases. Drugs are heavily regulated. Clinical trials on human subjects must show that a pharmaceutical drug is safe and effective for its intended use. Then, the drug must be manufactured under controlled conditions and packaged to meet strict labeling standards before it’s approved by the FDA for consumer use.

Unlike drugs, the FDA says that supplements are for nutritional purposes only. Because supplements are not considered drugs, they are not monitored in the same way. While the FDA does have some regulations for manufacturing and labeling, nutritional supplements have different guidelines for testing, safety, and efficacy than pharmaceutical drugs. Unlike drugs, supplements do not require pre-approval by the FDA before they are released for sale to the consumer.

How does this affect what supplements are allowed to claim?

The Dietary Supplement Health and Education Act of 1994 (DSHEA) defined the role of supplements and outlined what vitamin companies can legally say about their products. The act dictates that because supplements are not drugs, supplement companies cannot imply, insinuate or state that their product diagnoses, treats, cures, or prevents disease of any kind.

The FDA has further interpreted some normal conditions as disease precursors or markers. This is why you may see some vague wording about what a supplement does--it’s done to comply with FDA’s guidelines on approved dietary supplement claims.

The disclaimer shown above is mandatory for dietary supplements if they make any claims about affecting the structure and/or function of the human body - and the FDA enforces claims to make sure they are following approved guidelines for dietary supplement allowable claims.

Are any supplements approved by the FDA?

No. The FDA does not “approve” nutritional supplements because it does not approve foods. The FDA only approves pharmaceutical drug products.

The FDA does monitor supplement manufacturing and labeling, and regularly inspects companies to ensure that they are meeting regulations. If a supplement company does not comply with FDA regulations, the FDA can ban them from selling their product within the U.S

Additional L-Serine Research Links:

• Mechanisms of L-Serine Neuroprotection in vitro Includes ER Proteostasis Regulation
  Dunlop RA, Powell J, Guillemin GJ, Cox PA
  Neurotoxicity Research. 2018 Jan 1;33(1):123-32.

• L-Serine-Mediated Neuroprotection Includes the Upregulation of the ER Stress Chaperone Protein Disulfide Isomerase (PDI)
  Dunlop RA, Powell JT, Metcalf JS, Guillemin GJ, Cox PA
  Neurotoxicity Research. 2018 Jan 1;33(1):113-22.

• L-Serine: a Naturally-Occurring Amino Acid with Therapeutic Potential
  Metcalf JS, Dunlop RA, Powell JT, Banack SA, Cox PA
  Neurotoxicity Research. 2017 Sep 19:1-9.

• Studies of Environmental Risk Factors in Amyotrophic Lateral Sclerosis (ALS) and a Phase I Clinical Trial of  L-serine
  Bradley WG, Miller RX, Levine TD, Stommel EW, Cox PA
  Neurotoxicity Research. 2018 Jan 1;33(1):192-8

• Traditional Food Items in Ogimi, Okinawa: L-Serine Content and the Potential for Neuroprotection
  Cox PA, Metcalf JS
  Current Nutrition Reports. 2017 Mar 1;6(1):24-31.

• Phase I clinical trial of safety of L-serine for ALS patients
  Levine TD, Miller RG, Bradley WG, Moore DH, Saperstein DS, Flynn LE, Katz JS, Forshew DA, Metcalf JS, Banack SA, Cox PA
  Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. 2017 Jan 2;18(1-2):107-11.