Commercial production of vitamin C for fortification and dietary supplements

In most mammals, vitamin C is made in the liver from blood sugar using a four-step enzymatic process. Humans and about 20 other mammalian species lack one of these enzymes, requiring us to both obtain vitamin C from our diet and to sustain internal levels of vitamin C using a variety of other food antioxidants.

But rather than extracting vitamin C from foods, the modern way to manufacture it is to start with dextrose, a sugar identical to blood glucose, and manipulate it into ascorbic acid, which is vitamin C; mimicking the biological production technique to some extent. The result is a nature-identical vitamin indistinguishable from the form in foods.

The primary method of biosynthesizing vitamin C starts with the conversion of glucose into sorbitol. Dextrose is converted to sorbitol by adding hydrogen to the molecule; that is typically done with a catalyst (defined as an easily recoverable material that facilitates a chemical reaction but is not used up in the reaction nor added to the molecule). The only added element is hydrogen, which is applied in a pressure tank.

Converting the sorbitol into sorbose and then into an intermediate known as 2-KLG is done using a two-step fermentation process

Then a final lactonization step (reacting 2-KLG with acid and/or dehydration is used to produce the lactone known as l-ascorbic acid/vitamin C; chemical form C₆H₈O₆).

When to take products with enteric coating

The reason why we suggest taking enterically coated supplements on an empty stomach is to avoid the pill (capsule or tablet) being trapped in the stomach with food for an hour or more, which could allow the contents to release prematurely prior to reaching the small intestine.

In a study of 24 subjects, at baseline the median gastric pH was ∼1, increased to pH 4.5 with ingestion of the meal, and then returned to approximately pH 1 some 3–4 h after the start of the meal. https://journals.physiology.org/doi/full/10.1152/japplphysiol.00956.2001#:~:text=test%20(nonparametric).-,RESULTS,the%20start%20of%20the%20meal

However, if someone has low stomach acid (aging, antacids, etc.) to start, the pH can increase even more and risk the capsule emptying directly into the stomach. That can cause either degradation of the contents or increased risk of burping up and tasting any oils in the product. 

The esophagus and stomach are especially sensitive to essential oils, as evidenced by people adding drops to water and drinking that, later ending up with mucous lining degradation leading to stomach pain or heartburn, and occasionally emergency room visits.

Kosher for Passover means avoiding fermentation of grains

 

There are different interpretations of the religious laws, but in general they do not allow wheat or other traditional grains, including grain alcohol, during Passover with one exception:

Wheat flour that is used to make matzos has been specially supervised from harvest through processing to ensure that it has not had an opportunity to start fermenting, so it is continually inspected to ensure that it is not in contact with moisture in order to inhibit fermentation. The water used to make matzos is left out overnight to cool, also in order to inhibit fermentation. Milling, mixing with water, kneading, and baking are done in separate areas to avoid cross-contamination. 

Fermentation is believed to occur about 18 minutes after a grain is mixed with moisture, so after mixing the flour with water, kosher for Passover matzos are put in the oven within that time limit; the ovens are separate from the preparation areas so that the heat is not promoting fermentation of materials being mixed/prepared.

Grain-based fermentation products such as alcohol are also forbidden in kosher for Passover products, since the purpose is to avoid using aged or fermented materials to mimic the plight of fleeing slaves who didn't have time to let (sourdough) bread rise in their hurry to flee Egypt. 

(While it is quite likely that the newly freed slaves would have grabbed already-baked bread, this specific kosher for Passover practice of removing all leavened bread and other forbidden items from a household during the holiday is evidently intended as a ritual to evoke sympathy for their hurried exodus during the Passover Seders practiced by their descendants.)

The traditional grains banned unless following the same rules as the matzo wheat include wheat, rye, barley, oats, and spelt; all of which were available in Egypt some 3,500 years ago. 

Wine is allowed for Passover when the yeast is the product of the grapes themselves. But the wine must not include added non-kosher yeasts, other non-kosher additives (isinglass), or be produced/stored in a room containing grains or products made from grains. The work must also stop on the Sabbath, so observant Jews must be the winemakers. 

 I'll be doing a live webinar on Men's Health this Thursday at 5 PM Pacific time (7 PM Central)...

https://us06web.zoom.us/meeting/register/tZAtceyrpjgoGtOf_1bY_JfM0BuSbJJazl_C#/registration

 Neil will be on the radio Sunday morning 3/19/2023. It's Al Forman's Sav-A-Lot Nutrition Hour at 11am ET, 10 Central on WWNN radio 1470 AM; 95.3 FM in South Florida. Go to https://trueoldiesfla.com/podcasts/sav-a-lot-nutrition Listen live there, too; click on the Listen Live button under the station 95.3 FM at the top right of that page.

Also Neil's previous interviews with Al are available to listen or download as a podcast: https://sav-a-lotnutritioncenters.com/?s=Levin&lang=en

Federal Dietary Supplement Registry bills

 Dietary Supplement Legislation Misguided & Inflationary

A bill sponsored by Senators Durbin (D-IL) and Braun (R-IN) - S.4090, the Dietary Supplement Listing Act - mandates a registry of all dietary supplements, citing safety concerns. Meanwhile, the Senate Health, Education, Labor, and Pensions (HELP) Committee also added mandatory product registration for this non-drug category to must-pass prescription drug user fee legislation S.4348, the Food and Drug Administration Safety and Landmark Advancements Act of 2022 (FDASLA). 

These concerns are overblown; the proposed solution draconian. Why treat an overwhelmingly safe food category as inherently dangerous? Multivitamins, vitamin C, calcium, fish oil, and common nutrients are non-toxic, with few safety concerns.

Senator Durbin uses Adverse Event Reports (AERs) as justification. But Mr. Durbin knows AERs are defined as associative, not proof of a causal relationship. I manage a team handling dietary supplement AERs for a responsible manufacturer, which are promptly investigated and reported to the FDA. The few AERs we receive are typically caused by pre-existing conditions/known drug effects, not supplements. And many dietary supplement AERs received by FDA involve multivitamin choking issues, not toxicity. 

There are potential interactions between certain ingredients and certain drugs. A published report of Mayo Clinic patient records identified only five such ingredients, noting only minor negative drug interactions. Statistics from the authoritative American Association of Poison Control Centers confirm zero deaths are associated with dietary supplements most years. Official AERs, not necessarily caused by supplements, showed only 166 hospitalizations and 22 deaths over an 11-year, 4-month period. By contrast, CDC estimates 48 million illnesses, 128,000 hospitalizations, and 3,000 deaths from foodborne diseases each year; food allergies cause 15 million illnesses, 30,000 ER visits and 150–200 deaths. Taking a dietary supplement is statistically far safer than eating a meal. 

If there is a safety issue, FDA already has the power to ban products, as it did with the herb ephedra. Facility registration is already mandated in existing Bioterrorism and Food Safety laws, but S.4090 inexplicably removes carefully designed antiterrorist protections. The National Institutes of Health already have a huge dietary supplement label database, which the FDA seeks to duplicate in a wasteful agency rivalry. 

S.4090 imposes large fines - and jail terms - for not getting advance bureaucratic permission to market any supplement, even vitamin C. Companies must seek registration numbers and identify individuals to be severely penalized for infractions, with sales restricted by agency refusal or delay. Why does the FDA need absolute veto power over every vitamin; adding red tape and inflationary costs? The FDA already has statutory authority to inspect manufacturers, review labels and batch records, and confirm AERs are being properly handled/reported. Since the rationale is lack of enforcement of existing laws, how does piling on new regulations, fees, and harsh penalties solve that persistent agency problem? An analogy: would new laws lowering the speed limit and requiring drivers to keep mileage logs stop speeders, or is enforcement the real solution? 

The dietary supplement industry welcomes reasonable consumer protections. We supported laws giving FDA authority over ingredients, label claims, Good Manufacturing Practices (GMP), facility inspections, food safety practices, facility registration, adverse event reporting, steroid bans, and allergen labeling. We’ve repeatedly lobbied Congress for higher FDA enforcement budgets to weed out bad actors, but oppose universal pre-market approval.

Why is a safe food category – dietary supplements – targeted for harsh regulation and higher costs, strangling innovation and consumer needs? If safety is the issue, why shouldn’t riskier food manufacturers (allergens and food poisoning) also need pre-market approval, their employees targeted for prosecution and fines? This is a punitive bill targeting an overwhelmingly safe product category for no justifiable reason. 

Neil Edward Levin, CCN, DANLA

NOW Health Group

Bloomingdale, Illinois

North Macedonian medical conference presentation

 I'm giving a remote presentation tomorrow morning 5-20-2022 at the Macedonian Association of Internal Medicine conference https://internist2022.com/program/ I'm listed on page 7 of the program.