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. Author manuscript; available in PMC: 2021 Jul 13.
Published in final edited form as: CellR4 Repair Replace Regen Reprogram. 2018 Mar 19;6(1):e2493.

Can high-dose omega-3 fatty acids and high-dose vitamin D3 (cholecalciferol) prevent type 1 diabetes and sustain preservation of beta-cell function after disease onset?

C Ricordi 1,2,3,4,5, G Lanzoni 1,3,4
PMCID: PMC8276914  NIHMSID: NIHMS1056746  PMID: 34262992

Modulation of inflammation and immunity could prevent, delay or halt the progression of autoimmunity in Type 1 Diabetes (T1D). Vitamin D and omega-3 long chain polyunsaturated fatty acids (LCPUFA) could attain such modulation1,2. Contemporary administration of high dose vitamin D and omega-3 PUFA was recently tested in pilot clinical trials to determine if progression of auto-immunity could be halted following T1D onset3–5. The rationale for this combination strategy is that Omega 3 LCPUFA (eicosapentaenoic acid, EPA, and docosahexaenoic acid, DHA) and Vitamin D can have beneficial effects not only on inflammatory markers, but also on immunomodulation-increasing regulatory T cells (Tregs), while decreasing Th17 cells and Th1/Th2 ratios1,2. In contrast, arachidonic acid (AA) showed an opposite effect on Tregs, Th17 cells and Th1/Th2 ratios. A very high AA/EPA ratio has been observed in subjects diagnosed with T1D and other autoimmune conditions (F.Cadario and C. Ricordi, personal communication and manuscript in preparation). This may reflect a diet-related pro-inflammatory baseline condition. This condition could predispose to or trigger the subsequent development of autoimmunity. In this direction, anti-inflammatory nutrition could have an important synergistic role, in addition to Vitamin D and Omega 3 LCPUFA supplementation, as already explored by Cadario and collaborators in pilot and ongoing clinical trials. If the initial results will be confirmed, similar strategies to reduce exogenous insulin requirements and promote persistence of residual endogenous insulin production could be of assistance to reduce the risk of complications in T1D6–9.

The recently reported maintenance of C-peptide production above baseline for over 2 years post diagnosis5 is very encouraging and warrants randomized controlled trials. Additional mechanistic studies, including assessment of cytokine profiles and inflammatory markers, will be required to determine the effect of the proposed combination therapy for prevention of T1D, as well as for preservation of beta-cell mass and function in patients with recent onset of T1D.

Because of the significant interest raised by these preliminary results, the 1st PreDiRe T1D (Preventing Disease and its Recurrence in Type 1 Diabetes) Symposium was organized to discuss initial results, possible alternatives and complementary combination strategies, to eventually generate consensus on the possibility to extend these interventions to disease prevention strategies (Figure 1).

Figure 1.

Figure 1.

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In summary, the use of combination high-dose omega-3 LCPUFA and high-dose vitamin D3 (Cholecalciferol) therapy has been well tolerated in pilot trials and may have beneficial effects on the maintenance of beta-cell function before and after T1D onset. Randomized controlled trials are required to validate this hypothesis and initial clinical results. Similar combination therapies aimed at modulating inflammation and promoting immunomodulation may be tested to prevent, reverse, or halt the progression of other autoimmune diseases.

In this issue of CellR4, we share the protocol for the Poseidon Clinical Trial (Pilot Study of OMEGA-3 and Vitamin D in High-Dose in Type I Diabetic Patients, ClinicalTrials.gov Identifier: NCT03406897), recently allowed by the FDA. Its availability in open access could facilitate implementation by interested physicians and centers, and could stimulate the use of a similar design in the context of other autoimmune diseases.

References

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